Cancerous tumors are the subject of numerous treatment methodologies depending on the types and locations of the tumors. The primary methodologies involve surgical excision of the tumor, radiology, or chemotherapy typically delivered intravenously to a patient. One result of intravenous (IV) chemotherapy is that the chemotherapy substance is delivered throughout the patient's entire body with significant and deleterious side effects being suffered by the patient. Ideally, cancerous tissues are desired to be treated locally, or in situ, to the individual tumors thereby minimizing the exposure of the patients body to any adverse effects of the treatment.
In situ tumor destruction with cryogenics, radiofrequency or laser ablation has received increasing attention as a treatment modality for focal cancer such as liver, lung, pancreas, prostate, breast, node, and kidney. However, a number of recurrences at sites of ablation are seen from 10% to 40% for cryogenic treatment. Additionally an increased use of combined therapies with these ablative methods, such as chemotherapy, radiotherapy and immunotherapy, are aiming at optimizing their safety and local efficacy. They can also potentially increase the overall survival, and the host defense against micro-metastatic disease, or distant metastases.
A number of therapeutic substances such as drugs, chemical, protein, biologic or cell, and injection techniques are in use along with various strategies to combine their administration with that of the focal ablative technique. For instance, cryoablation (i.e. the in situ destruction of tissue by deep freezing with cryogenic applicators such as cryoprobes or cryoneedles) has been combined with systemic (IV) or regional, Intra Arterial (IA), chemotherapeutics or local chemical (such as ethanol, EtOH) injection to improve local ablative results, particularly for large tumors or tumors located in the vicinity of risky structures as disclosed in U.S. Pat. No. 7,344,530 to Bischof. Some of the therapeutic substances are mixtures of drugs in solution, suspension or emulsion that may include drug carriers, vectors, radiocontrast agents or dye that serve as markers or tracers for assessing drug distribution and clearance during image-guided interventions.
A great number of thermal or cryothermal devices exist already that are able to deliver energy to target tissue within small instruments so that they can be used for various minimally invasive (MIS) approaches (percutaneous, endoscopic, endovascular catheter) or through natural orifices and open surgery. In a purely scientific sense, energy delivery means the addition of energy resulting in an increase in the thermal profile of the tissue. As used herein, energy delivery is defined as meaning energy transfer to or from the subject tissue resulting in an elevation of tissue temperature (addition of energy) or a cooling of the tissue temperature (removal of energy).
An even greater number of perfusion devices for perfusing, infusing or injecting drugs or substances within the patient's body or within target tissue exist already. They are needle-like (rigid, semi-rigid or formable shaft) or catheter-like (flexible shaft). A preferred method for perfusing a tumor with a drug is to directly inject the therapeutic substance within the interstitial compartment of the tumor to maximize its effectiveness and minimize its systemic side effects. These methods, such as chemoablation, intra tumor (IT), or intralesional (IL) therapy, are growing in use since they have many advantages such as: Narrow therapeutic index drugs can be safely injected and at a much higher concentration than when systemically injected. Also, drugs can be injected in brain tumors that could not otherwise penetrate the blood brain barrier. These techniques are minimally invasive, less aggressive, and less costly than open surgery, to cite only a few.
Various methods for combining the focal energy delivery with the administration of therapeutic fluids, drugs or substances have been designed. These methods generally administer the drug before or after the delivery of energy (U.S. Pat. No. 7,083,612 B2 to Littrup), either systemically, regionally or locally (interstitially). U.S. Publication 2008/0027419A1 to Hamel et al. shows a delivery device for a treatment agent that combines a cryoprobe and a sealed delivery device provided with a puncture member to break the seal. Such a device does not allow for any control of the substance flow based on the change of physical state of the substance—i.e. liquid to solid and vice versa—and prevention of reflux during injection within tissue based on the physical change of state of the tissue water and structure. In addition, there is no provision for sensing a critical parameter such as fluid pressure before, during, and after substance delivery that allows for fine control of fluid substance delivery. There is no provision for a system that would timely control the cooling and delivery sequences necessary for successfully injecting the substance into tissue.
Although the interstitial injection of drugs and substances has shown some potential advantages, it has not been yet fully exploited. For instance, fluids are injected around the region of energy delivery to protect sensitive structures from unwanted harmful effect. For example, saline can be injected during cryogenic-mediated breast tumor ablation to protect the skin from freezing. Other examples of fluid injection include the sensitization of the tissue to thermal ablation, and for instances with injection of saline for increasing the area of thermal ablation during energy deposition with a radio frequency (RF) device, or with sensitizing drugs as disclosed in U.S. Pat. No. 7,344,530 to Bischof. Multiple Studies demonstrate that the interstitial distribution and retention, i.e. residence time of a drug substance injected systemically (IV) or regionally (IA) would be improved with the simultaneous administration of the drug and the energy, along with a potential for better safety and effectiveness. Additionally, such combinations could also activate the host immune response against local and disseminated cancer cells. For instances during cryosurgery and simultaneous local injection of a drug in a fluid form in the vicinity of the frozen tissue the forces exerted on the fluid flow and the resulting tissue structural changes pave the way for driving or transporting substances within an interstitial matrix, for increasing cell membrane permeation to the substance, and for modifying the extracellular matrix porosity (i.e. the pore structure) resulting in an improved substance retention or residence time like into the mesh of a net. Some of these thermo-mechanical changes result in prevention of backflow of the substance along the needle track, along with convective flow of the substance ahead of the ice front during cryosurgery. However, due to the shortcomings of existing perfusion needles, such as incapability of maintaining the substance in a liquid state or at their temperature range of structural integrity during the administration of heat energy or the deprivation of heat energy (cooling), there is an inability to perform the interstitial injections during and in the close vicinity of the energy delivery devices. For instance, most cytotoxic drugs can be combined with cryoablation but their flow will stop when the temperature of the injection needle wall drops to their freezing point, i.e. about 0° C., and they will be denaturated by thermal shock (sudden drop of temperature followed by temperature rise), particularly if they are made of proteins or cells, when in contact with a cooling source such as a cryoneedle or cryoprobe.
Therefore there is a need for a tissue perfusion needle that can maintain the flowability and structural integrity of a substance during its transfer through the needle lumen until it is interstitially delivered to the target tissue concurrently submitted to focal cryoablation.
During an operative procedure the perfusion needle is guided (utilizing direct vision or other imaging methods such as CT, MR, US, etc.) to a location that is thought as best for optimal drug distribution and drug permeation over the target tissue. However, there is no assurance that the elected site of drug delivery is best for optimal delivery. It is known that a fibrous tissue is more difficult to permeate than a soft tissue and that a low interstitial pressure is better than a high pressure for the drug bulk flow. Consequently, it would be useful to know beforehand whether the site of injection is at relatively high or low pressure. The relative pressure being a parameter that would help initiating perfusion at injection or infusion pressure that would be slightly grander.
Therefore, there is a need for a sensing method for the perfusion procedure that would detect the perfusion needle patency, the proper needle priming, absence of air, change of substance physical state and the tissue target pressure at all times before, during and after a procedure.
There is an unmet need for a needle to deliver the substance at a time and location when the tissue is under cryoablative therapy, partially or wholly frozen and when an unfrozen part of such tissue should be permeated with the fluid substance.
There is also an unmet need for such a needle to sense the moment when in the course of the cryoablative process the substance is still in a liquid and injectable state, even though the needle is immersed within the frozen tissue.
There is also a need for a combined cryoablative and substance injection method that is based on the target calculated volume, target location, target shape or characteristics. A method that specifies the location, number, characteristics of the injection needle and needle tip (deployable, multi-hole and side hole tip, tip bevel, echogenicity), the injection sites, rate and the substance characteristics or temperature, so that the liquid substance flow, distribution and retention are optimized, to insure a homogeneous and complete permeation of the target with the diagnostic/therapeutic substance.